UOG Journal Club: November 2017

Outcome of monochorionic twin pregnancy with selective intrauterine growth

restriction according to umbilical artery Doppler flow pattern of smaller twin:
systematic review and meta-analysis

D. Buca, G. Pagani, G. Rizzo, A. Familiari, M.E. Flacco, L. Manzoli, M. Liberati,

F. Fanfani, G. Scambia and F. DAntonio

Volume 50, Issue 5, pages 559-568

Journal Club slides prepared by Dr Yael Raz

(UOG Editor for Trainees)
 Outcome in MC twin pregnancy affected by sIUGR according to UA Doppler flow pattern
Buca et al. UOG 2017

Introduction
Gratacs et al.1 classification of sIUGR in MC twins, based on umbilical artery (UA)
Doppler flow pattern of the smaller twin :
Type I - persistently positive diastolic flow
Type II - persistently absent/reversed diastolic flow
Type III - intermittently absent/reversed diastolic flow

Stated perinatal outcomes in the original series :

- Type I sIUGR showed the best outcome
- Type II had the worst prognosis
- Type III was characterized by an unpredictable clinical course.
1GratacsE, Lewi L, Muoz B, Acosta-Rojas R, Hernandez-Andrade E, Martinez JM, Carreras E, Deprest J. A classification system for selective intrauterine growth restriction in
monochorionic pregnancies according to umbilical artery Doppler flow in the smaller twin. Ultrasound Obstet Gynecol 2007; 30: 2834.
 Outcome in MC twin pregnancy affected by sIUGR according to UA Doppler flow pattern
Buca et al. UOG 2017

Aim of the systemic review

To explore the outcome in MC twin pregnancies affected by

sIUGR according to the UA Doppler flow pattern of the
smaller twin.
 Outcome in MC twin pregnancy affected by sIUGR according to UA Doppler flow pattern
Buca et al. UOG 2017

Methods Study selection

Inclusion: studies reporting the prenatal diagnosis of sIUGR in MC
twins according to the classification of Gratacs et al.

Exclusion: - Cases with superimposed TTTS

- Studies reporting only one type of sIUGR
- Studies from which the information regarding the
type of sIUGR could not be extrapolated
- Studies including cases undergoing fetal therapy
- Studies published before 2000
Outcome in MC twin pregnancy affected by sIUGR according to UA Doppler flow pattern
Buca et al. UOG 2017

Results - Study design

13 studies were included -

610 MC twin pregnancies affected by
sIUGR:
39% Type I
38.2 % - Type II
22.8% - Type III

Mean gestational age at diagnosis:

Type I - 26.5 weeks
Type II - 21.1 weeks
Type III - 20.2 weeks
 Outcome in MC twin pregnancy affected by sIUGR according to UA Doppler flow pattern
Buca et al. UOG 2017

Results - Pooled proportions for outcomes examined

Perinatal mortality :
Type I - 4.1%
Type II - 16.1%
Type III - 11.5%

IUFD :
Type I - 3.1%
Type II - 11%
Type III - 9.6%

Double fetal loss :

Type I 1.9%
Type II - 7%
Type III - 4.9%
 Outcome in MC twin pregnancy affected by sIUGR according to UA Doppler flow pattern
Buca et al. UOG 2017

Results - Pooled odds ratios for outcomes examined

Perinatal mortality,
IUFD,
Neonatal death,
Double fetal loss:

Type II >Type I sIUGR

No difference among the other

variants.
 Outcome in MC twin pregnancy affected by sIUGR according to UA Doppler flow pattern
Buca et al. UOG 2017

Results - Pooled odds ratios for outcomes examined

for smaller and larger fetuses

Perinatal mortality :
Type II sIUGR -significantly
higher in the growth-restricted
fetus compared with the larger
twin (OR, 2.4)
Types I and III - no difference.
 Outcome in MC twin pregnancy affected by sIUGR according to UA Doppler flow pattern
Buca et al. UOG 2017

Results - Morbidity
Abnormal postnatal brain imaging:
Twins affected by Type II (OR, 4.9 ) or Type III (OR, 8.2) sIUGR had a
significantly higher risk of compared with Type I sIUGR.
No difference in the growth-restricted compared with the larger twin for all
sIUGR types.

IVH and PVL:

Both were significantly higher in Type II compared with Type I sIUGR,
(OR, 10.6 and 4.4, respectively).
No increased risk in either IVH or PVL in Type II compared with Type III.

NICU admission:
Risk was higher in Type II compared with Type I sIUGR (OR, 18.3).
No difference between Type II vs III and Type I vs III sIUGR.
Not difference between the smaller and larger twins for all sIUGR types.
 Outcome in MC twin pregnancy affected by sIUGR according to UA Doppler flow pattern
Buca et al. UOG 2017

Results - Morbidity
Composite adverse outcome:
Risk was higher in Type II (OR, 4.9) and Type III (OR, 5.1) compared with Type I
sIUGR.
No difference between Type II and Type III sIUGR.

Deterioration of fetal status:

Risk was higher in Type II compared with Type I (OR, 7.2 ) and Type III (OR, 16.1).
No difference in risk in Type I vs III sIUGR.

Mean gestational age at delivery:

Twin pregnancies affected by Type I sIUGR were delivered at a significantly later
gestational age than those with Type II (33.7 vs 34.3 weeks; MD, 2.8 weeks) and
Type III (33.7 vs 30.9 weeks; MD, 2.1 weeks).
No difference in gestational age at delivery between Type II and Type III sIUGR.
 Outcome in MC twin pregnancy affected by sIUGR according to UA Doppler flow pattern
Buca et al. UOG 2017

Main findings
Type II sIUGR is at a higher risk of perinatal mortality and morbidity, abnormal
postnatal brain imaging and admission to NICU compared to Type I

The likelihood of an abnormal outcome is usually not significantly different

between Types II and III.

Type III sIUGR is affected by an unpredictable clinical course.

Pregnancies affected by Types II and III sIUGR are delivered at a significantly

earlier gestational age than those affected by Type I.

Pregnancies affected by Type II have a higher degree of BW discordance

compared with Types I and III.
 Outcome in MC twin pregnancy affected by sIUGR according to UA Doppler flow pattern
Buca et al. UOG 2017

Limitations
Small number of cases in some of the included studies.
Retrospective non-randomized design in some of the included studies.
Heterogeneity in prenatal management - data may be largely affected by
the different protocols rather than the natural history of the condition.
Different periods of follow up.
Most of the observed outcomes were reported by only a limited proportion
of the included studies preventing the stratification of the analysis
according to different gestational ages at presentation of sIUGR, type of
UA flow abnormality (absent vs reversed end-diastolic flow) and different
subtypes of neuromorbidity.
 Outcome in MC twin pregnancy affected by sIUGR according to UA Doppler flow pattern
Buca et al. UOG 2017

Conclusions Implications for clinical practice

Type I sIUGR:
Most likely represents the milder spectrum of growth restriction in MC twins.

The degree of unequal placental sharing between the twins is smaller than for the
other types of sIUGR, thus precluding a large discrepancy in fetal size. The
relatively small number of arterioarterial anastomoses compared with the other
sIUGR types allows relative hemodynamic stability between the twins, which is
reflected in the lower occurrence of perinatal death and postnatal brain damage

In the absence of Doppler abnormalities - follow up conservatively with

weekly ultrasound scans.
 Outcome in MC twin pregnancy affected by sIUGR according to UA Doppler flow pattern
Buca et al. UOG 2017

Conclusions Implications for clinical practice

Type II sIUGR:
These pregnancies are affected commonly by severe discordance in fetal weight and by
progressive abnormalities in arterial and venous Doppler, requiring delivery at an earlier
gestational age. However, the latency between onset of UA flow anomalies and delivery is
usually longer than that in singleton and dichorionic twin gestations.

The optimal prenatal management should be tailored according to the gestational age at
diagnosis, the degree of fetal weight discordance and the severity of Doppler abnormalities.

Follow up with biweekly scans in the presence of absent or reversed end-diastolic

flow in the UA, followed by delivery when venous Doppler abnormalities occur.
(Confirmation in prospective trial is required.)

Prenatal therapy (cord occlusion, laser coagulation of placental anastomoses) can be

considered before viability. (Relatively high rate of cotwin loss or maternal complications,
and is technically more difficult than when performed for TTTS).
 Outcome in MC twin pregnancy affected by sIUGR according to UA Doppler flow pattern
Buca et al. UOG 2017

Conclusions Implications for clinical practice

Type III sIUGR:
Type III sIUGR is characterized by the presence of intermittent absent or reversed end-
diastolic flow in the UA of the smaller twin, due to the peculiar vascular arrangement of Type
III sIUGR placentae, which show significantly more large arterioarterial anastomoses
compared with uncomplicated Types I and II sIUGR twins.

The clinical course of pregnancies with Type III sIUGR is mainly determined by the
magnitude and direction of blood exchange, which may lead to different clinical outcomes,
even in twins showing the same degree of growth discrepancy.

Type III sIUGR is affected by a high rate of unexpected fetal demise, even in the case of
stable Doppler findings, thus questioning the actual role of Doppler ultrasound.

Management of Type III sIUGR is arbitrary; several factors such as gestational age at
diagnosis, degree of growth discordance and severity of Doppler anomalies may help the
decision planning, but parents should be counseled about the unpredictable clinical
course of these pregnancies. Fetal therapy may be considered before viability.
 Outcome in MC twin pregnancy affected by sIUGR according to UA Doppler flow pattern
Buca et al. UOG 2017

Points for discussion

Is UA Doppler flow pattern also of value in MC twins without sIUGR?

Is UA Doppler flow pattern also of value in MC twins with discordancy?

Can early changes in UA Doppler flow pattern predict the later occurrence
of sIUGR?

Can MC twins with Type III sIUGR be better stratified by UA Doppler

flow?